28.
Prado-Lopez, S.; Conesa, A.; Arminan, A.; Martinez-Losa, M.; Escobedo-Lucea, C.; Gandia, C.; Tarazona, S.; Melguizo, D.; Blesa, D.; Montaner, D.; Sanz-Gonzalez, S.; Sepulveda, P.; Goetz, S.; O'Connor, J. Enrique; Moreno, R.; Dopazo, J.; Burks, D. J.; Stojkovic, M.
Hypoxia Promotes Efficient Differentiation of Human Embryonic Stem Cells to Functional Endothelium Journal Article
In: STEM CELLS, vol. 28, no. 3, pp. 407-418, 2010, ISSN: 1066-5099.
@article{ISI:000277093700004,
title = {Hypoxia Promotes Efficient Differentiation of Human Embryonic Stem Cells
to Functional Endothelium},
author = { S. Prado-Lopez and A. Conesa and A. Arminan and M. Martinez-Losa and C. Escobedo-Lucea and C. Gandia and S. Tarazona and D. Melguizo and D. Blesa and D. Montaner and S. Sanz-Gonzalez and P. Sepulveda and S. Goetz and J. Enrique O'Connor and R. Moreno and J. Dopazo and D. J. Burks and M. Stojkovic},
url = {http://dx.doi.org/10.1002/stem.295},
doi = {10.1002/stem.295},
issn = {1066-5099},
year = {2010},
date = {2010-03-01},
journal = {STEM CELLS},
volume = {28},
number = {3},
pages = {407-418},
abstract = {Early development of mammalian embryos occurs in an environment of
relative hypoxia. Nevertheless, human embryonic stem cells (hESC), which
are derived from the inner cell mass of blastocyst, are routinely
cultured under the same atmospheric conditions (21% O(2)) as somatic
cells. We hypothesized that O2 levels modulate gene expression and
differentiation potential of hESC, and thus, we performed gene profiling
of hESC maintained under normoxic or hypoxic (1% or 5% O(2))
conditions. Our analysis revealed that hypoxia downregulates expression
of pluripotency markers in hESC but increases significantly the
expression of genes associated with angio-and vasculogenesis including
vascular endothelial growth factor and angiopoitein-like proteins.
Consequently, we were able to efficiently differentiate hESC to
functional endothelial cells (EC) by varying O(2) levels; after 24 hours
at 5% O(2), more than 50% of cells were CD34+. Transplantation of
resulting endothelial-like cells improved both systolic function and
fractional shortening in a rodent model of myocardial infarction.
Moreover, analysis of the infarcted zone revealed that transplanted EC
reduced the area of fibrous scar tissue by 50%. Thus, use of hypoxic
conditions to specify the endothelial lineage suggests a novel strategy
for cellular therapies aimed at repair of damaged vasculature in
pathologies such as cerebral ischemia and myocardial infarction. STEM
CELLS 2010; 28: 407-418},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Early development of mammalian embryos occurs in an environment of
relative hypoxia. Nevertheless, human embryonic stem cells (hESC), which
are derived from the inner cell mass of blastocyst, are routinely
cultured under the same atmospheric conditions (21% O(2)) as somatic
cells. We hypothesized that O2 levels modulate gene expression and
differentiation potential of hESC, and thus, we performed gene profiling
of hESC maintained under normoxic or hypoxic (1% or 5% O(2))
conditions. Our analysis revealed that hypoxia downregulates expression
of pluripotency markers in hESC but increases significantly the
expression of genes associated with angio-and vasculogenesis including
vascular endothelial growth factor and angiopoitein-like proteins.
Consequently, we were able to efficiently differentiate hESC to
functional endothelial cells (EC) by varying O(2) levels; after 24 hours
at 5% O(2), more than 50% of cells were CD34+. Transplantation of
resulting endothelial-like cells improved both systolic function and
fractional shortening in a rodent model of myocardial infarction.
Moreover, analysis of the infarcted zone revealed that transplanted EC
reduced the area of fibrous scar tissue by 50%. Thus, use of hypoxic
conditions to specify the endothelial lineage suggests a novel strategy
for cellular therapies aimed at repair of damaged vasculature in
pathologies such as cerebral ischemia and myocardial infarction. STEM
CELLS 2010; 28: 407-418
relative hypoxia. Nevertheless, human embryonic stem cells (hESC), which
are derived from the inner cell mass of blastocyst, are routinely
cultured under the same atmospheric conditions (21% O(2)) as somatic
cells. We hypothesized that O2 levels modulate gene expression and
differentiation potential of hESC, and thus, we performed gene profiling
of hESC maintained under normoxic or hypoxic (1% or 5% O(2))
conditions. Our analysis revealed that hypoxia downregulates expression
of pluripotency markers in hESC but increases significantly the
expression of genes associated with angio-and vasculogenesis including
vascular endothelial growth factor and angiopoitein-like proteins.
Consequently, we were able to efficiently differentiate hESC to
functional endothelial cells (EC) by varying O(2) levels; after 24 hours
at 5% O(2), more than 50% of cells were CD34+. Transplantation of
resulting endothelial-like cells improved both systolic function and
fractional shortening in a rodent model of myocardial infarction.
Moreover, analysis of the infarcted zone revealed that transplanted EC
reduced the area of fibrous scar tissue by 50%. Thus, use of hypoxic
conditions to specify the endothelial lineage suggests a novel strategy
for cellular therapies aimed at repair of damaged vasculature in
pathologies such as cerebral ischemia and myocardial infarction. STEM
CELLS 2010; 28: 407-418
27.
Rattei, T.; Tischler, P.; Goetz, S.; Jehl, M.; Hoser, J.; Arnold, R.; Conesa, A.; Mewes, H.
SIMAP-a comprehensive database of pre-calculated protein sequence similarities, domains, annotations and clusters Journal Article
In: NUCLEIC ACIDS RESEARCH, vol. 38, no. 1, pp. D223-D226, 2010, ISSN: 0305-1048.
@article{ISI:000276399100033,
title = {SIMAP-a comprehensive database of pre-calculated protein sequence
similarities, domains, annotations and clusters},
author = { T. Rattei and P. Tischler and S. Goetz and M. Jehl and J. Hoser and R. Arnold and A. Conesa and H. Mewes},
url = {http://dx.doi.org/10.1093/nar/gkp949},
doi = {10.1093/nar/gkp949},
issn = {0305-1048},
year = {2010},
date = {2010-01-01},
journal = {NUCLEIC ACIDS RESEARCH},
volume = {38},
number = {1},
pages = {D223-D226},
abstract = {The prediction of protein function as well as the reconstruction of
evolutionary genesis employing sequence comparison at large is still the
most powerful tool in sequence analysis. Due to the exponential growth
of the number of known protein sequences and the subsequent quadratic
growth of the similarity matrix, the computation of the Similarity
Matrix of Proteins (SIMAP) becomes a computational intensive task. The
SIMAP database provides a comprehensive and up-to-date precalculation of
the protein sequence similarity matrix, sequence-based features and
sequence clusters. As of September 2009, SIMAP covers 48 million
proteins and more than 23 million non-redundant sequences. Novel
features of SIMAP include the expansion of the sequence space by
including databases such as ENSEMBL as well as the integration of
metagenomes based on their consistent processing and annotation.
Furthermore, protein function predictions by Blast2GO are pre-calculated
for all sequences in SIMAP and the data access and query functions have
been improved. SIMAP assists biologists to query the up-to-date sequence
space systematically and facilitates large-scale downstream projects in
computational biology. Access to SIMAP is freely provided through the
web portal for individuals (http://mips.gsf.de/simap/) and for
programmatic access through DAS (http://webclu.bio.wzw.tum.de/das/) and
Web-Service
(http://mips.gsf.de/webservices/services/SimapService2.0?wsdl).},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The prediction of protein function as well as the reconstruction of
evolutionary genesis employing sequence comparison at large is still the
most powerful tool in sequence analysis. Due to the exponential growth
of the number of known protein sequences and the subsequent quadratic
growth of the similarity matrix, the computation of the Similarity
Matrix of Proteins (SIMAP) becomes a computational intensive task. The
SIMAP database provides a comprehensive and up-to-date precalculation of
the protein sequence similarity matrix, sequence-based features and
sequence clusters. As of September 2009, SIMAP covers 48 million
proteins and more than 23 million non-redundant sequences. Novel
features of SIMAP include the expansion of the sequence space by
including databases such as ENSEMBL as well as the integration of
metagenomes based on their consistent processing and annotation.
Furthermore, protein function predictions by Blast2GO are pre-calculated
for all sequences in SIMAP and the data access and query functions have
been improved. SIMAP assists biologists to query the up-to-date sequence
space systematically and facilitates large-scale downstream projects in
computational biology. Access to SIMAP is freely provided through the
web portal for individuals (http://mips.gsf.de/simap/) and for
programmatic access through DAS (http://webclu.bio.wzw.tum.de/das/) and
Web-Service
(http://mips.gsf.de/webservices/services/SimapService2.0?wsdl).
evolutionary genesis employing sequence comparison at large is still the
most powerful tool in sequence analysis. Due to the exponential growth
of the number of known protein sequences and the subsequent quadratic
growth of the similarity matrix, the computation of the Similarity
Matrix of Proteins (SIMAP) becomes a computational intensive task. The
SIMAP database provides a comprehensive and up-to-date precalculation of
the protein sequence similarity matrix, sequence-based features and
sequence clusters. As of September 2009, SIMAP covers 48 million
proteins and more than 23 million non-redundant sequences. Novel
features of SIMAP include the expansion of the sequence space by
including databases such as ENSEMBL as well as the integration of
metagenomes based on their consistent processing and annotation.
Furthermore, protein function predictions by Blast2GO are pre-calculated
for all sequences in SIMAP and the data access and query functions have
been improved. SIMAP assists biologists to query the up-to-date sequence
space systematically and facilitates large-scale downstream projects in
computational biology. Access to SIMAP is freely provided through the
web portal for individuals (http://mips.gsf.de/simap/) and for
programmatic access through DAS (http://webclu.bio.wzw.tum.de/das/) and
Web-Service
(http://mips.gsf.de/webservices/services/SimapService2.0?wsdl).
26.
Brumos, J.; Colmenero-Flores, J. M.; Conesa, A.; Izquierdo, P.; Sanchez, G.; Iglesias, D. J.; Lopez-Climent, M. F.; Gomez-Cadenas, A.; Talon, M.
In: FUNCTIONAL & INTEGRATIVE GENOMICS, vol. 9, no. 3, pp. 293-309, 2009, ISSN: 1438-793X.
@article{ISI:000267339600003,
title = {Membrane transporters and carbon metabolism implicated in chloride
homeostasis differentiate salt stress responses in tolerant and
sensitive Citrus rootstocks},
author = { J. Brumos and J. M. Colmenero-Flores and A. Conesa and P. Izquierdo and G. Sanchez and D. J. Iglesias and M. F. Lopez-Climent and A. Gomez-Cadenas and M. Talon},
url = {http://dx.doi.org/10.1007/s10142-008-0107-6},
doi = {10.1007/s10142-008-0107-6},
issn = {1438-793X},
year = {2009},
date = {2009-08-01},
journal = {FUNCTIONAL & INTEGRATIVE GENOMICS},
volume = {9},
number = {3},
pages = {293-309},
abstract = {Salinity tolerance in Citrus is strongly related to leaf chloride
accumulation. Both chloride homeostasis and specific genetic responses
to Cl(-) toxicity are issues scarcely investigated in plants. To
discriminate the transcriptomic network related to Cl(-) toxicity and
salinity tolerance, we have used two Cl(-) salt treatments (NaCl and
KCl) to perform a comparative microarray approach on two Citrus
genotypes, the salt-sensitive Carrizo citrange, a poor Cl(-) excluder, and the tolerant Cleopatra mandarin, an efficient Cl(-) excluder. The
data indicated that Cl(-) toxicity, rather than Na(+) toxicity and/or
the concomitant osmotic perturbation, is the primary factor involved in
the molecular responses of citrus plant leaves to salinity. A number of
uncharacterized membrane transporter genes, like NRT1-2, were
differentially regulated in the tolerant and the sensitive genotypes, suggesting its potential implication in Cl(-) homeostasis. Analyses of
enriched functional categories showed that the tolerant rootstock
induced wider stress responses in gene expression while repressing
central metabolic processes such as photosynthesis and carbon
utilization. These features were in agreement with phenotypic changes in
the patterns of photosynthesis, transpiration, and stomatal conductance
and support the concept that regulation of transpiration and its
associated metabolic adjustments configure an adaptive response to
salinity that reduces Cl(-) accumulation in the tolerant genotype.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Salinity tolerance in Citrus is strongly related to leaf chloride
accumulation. Both chloride homeostasis and specific genetic responses
to Cl(-) toxicity are issues scarcely investigated in plants. To
discriminate the transcriptomic network related to Cl(-) toxicity and
salinity tolerance, we have used two Cl(-) salt treatments (NaCl and
KCl) to perform a comparative microarray approach on two Citrus
genotypes, the salt-sensitive Carrizo citrange, a poor Cl(-) excluder, and the tolerant Cleopatra mandarin, an efficient Cl(-) excluder. The
data indicated that Cl(-) toxicity, rather than Na(+) toxicity and/or
the concomitant osmotic perturbation, is the primary factor involved in
the molecular responses of citrus plant leaves to salinity. A number of
uncharacterized membrane transporter genes, like NRT1-2, were
differentially regulated in the tolerant and the sensitive genotypes, suggesting its potential implication in Cl(-) homeostasis. Analyses of
enriched functional categories showed that the tolerant rootstock
induced wider stress responses in gene expression while repressing
central metabolic processes such as photosynthesis and carbon
utilization. These features were in agreement with phenotypic changes in
the patterns of photosynthesis, transpiration, and stomatal conductance
and support the concept that regulation of transpiration and its
associated metabolic adjustments configure an adaptive response to
salinity that reduces Cl(-) accumulation in the tolerant genotype.
accumulation. Both chloride homeostasis and specific genetic responses
to Cl(-) toxicity are issues scarcely investigated in plants. To
discriminate the transcriptomic network related to Cl(-) toxicity and
salinity tolerance, we have used two Cl(-) salt treatments (NaCl and
KCl) to perform a comparative microarray approach on two Citrus
genotypes, the salt-sensitive Carrizo citrange, a poor Cl(-) excluder, and the tolerant Cleopatra mandarin, an efficient Cl(-) excluder. The
data indicated that Cl(-) toxicity, rather than Na(+) toxicity and/or
the concomitant osmotic perturbation, is the primary factor involved in
the molecular responses of citrus plant leaves to salinity. A number of
uncharacterized membrane transporter genes, like NRT1-2, were
differentially regulated in the tolerant and the sensitive genotypes, suggesting its potential implication in Cl(-) homeostasis. Analyses of
enriched functional categories showed that the tolerant rootstock
induced wider stress responses in gene expression while repressing
central metabolic processes such as photosynthesis and carbon
utilization. These features were in agreement with phenotypic changes in
the patterns of photosynthesis, transpiration, and stomatal conductance
and support the concept that regulation of transpiration and its
associated metabolic adjustments configure an adaptive response to
salinity that reduces Cl(-) accumulation in the tolerant genotype.
25.
Nueda, M. Jose; Sebastian, P.; Tarazona, S.; Garcia-Garcia, F.; Dopazo, J.; Ferrer, A.; Conesa, A.
Functional assessment of time course microarray data Journal Article
In: BMC BIOINFORMATICS, vol. 10, 2009, ISSN: 1471-2105, (European Molecular Biology Network Conference, Martina, ITALY, SEP 18-20, 2008).
@article{ISI:000267522200009,
title = {Functional assessment of time course microarray data},
author = { M. Jose Nueda and P. Sebastian and S. Tarazona and F. Garcia-Garcia and J. Dopazo and A. Ferrer and A. Conesa},
url = {http://dx.doi.org/10.1186/1471-2105-10-S6-S9},
doi = {10.1186/1471-2105-10-S6-S9},
issn = {1471-2105},
year = {2009},
date = {2009-01-01},
journal = {BMC BIOINFORMATICS},
volume = {10},
abstract = {Motivation: Time-course microarray experiments study the progress of
gene expression along time across one or several experimental
conditions. Most developed analysis methods focus on the clustering or
the differential expression analysis of genes and do not integrate
functional information. The assessment of the functional aspects of
time-course transcriptomics data requires the use of approaches that
exploit the activation dynamics of the functional categories to where
genes are annotated.
Methods: We present three novel methodologies for the functional
assessment of time-course microarray data. i) maSigFun derives from the
maSigPro method, a regression-based strategy to model time-dependent
expression patterns and identify genes with differences across series.
maSigFun fits a regression model for groups of genes labeled by a
functional class and selects those categories which have a significant
model. ii) PCA-maSigFun fits a PCA model of each functional
class-defined expression matrix to extract orthogonal patterns of
expression change, which are then assessed for their fit to a
time-dependent regression model. iii) ASCA-functional uses the ASCA
model to rank genes according to their correlation to principal time
expression patterns and assess functional enrichment on a GSA fashion.
We used simulated and experimental datasets to study these novel
approaches. Results were compared to alternative methodologies.
Results: Synthetic and experimental data showed that the different
methods are able to capture different aspects of the relationship
between genes, functions and co-expression that are biologically
meaningful. The methods should not be considered as competitive but they
provide different insights into the molecular and functional dynamic
events taking place within the biological system under study.},
note = {European Molecular Biology Network Conference, Martina, ITALY, SEP
18-20, 2008},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Motivation: Time-course microarray experiments study the progress of
gene expression along time across one or several experimental
conditions. Most developed analysis methods focus on the clustering or
the differential expression analysis of genes and do not integrate
functional information. The assessment of the functional aspects of
time-course transcriptomics data requires the use of approaches that
exploit the activation dynamics of the functional categories to where
genes are annotated.
Methods: We present three novel methodologies for the functional
assessment of time-course microarray data. i) maSigFun derives from the
maSigPro method, a regression-based strategy to model time-dependent
expression patterns and identify genes with differences across series.
maSigFun fits a regression model for groups of genes labeled by a
functional class and selects those categories which have a significant
model. ii) PCA-maSigFun fits a PCA model of each functional
class-defined expression matrix to extract orthogonal patterns of
expression change, which are then assessed for their fit to a
time-dependent regression model. iii) ASCA-functional uses the ASCA
model to rank genes according to their correlation to principal time
expression patterns and assess functional enrichment on a GSA fashion.
We used simulated and experimental datasets to study these novel
approaches. Results were compared to alternative methodologies.
Results: Synthetic and experimental data showed that the different
methods are able to capture different aspects of the relationship
between genes, functions and co-expression that are biologically
meaningful. The methods should not be considered as competitive but they
provide different insights into the molecular and functional dynamic
events taking place within the biological system under study.
gene expression along time across one or several experimental
conditions. Most developed analysis methods focus on the clustering or
the differential expression analysis of genes and do not integrate
functional information. The assessment of the functional aspects of
time-course transcriptomics data requires the use of approaches that
exploit the activation dynamics of the functional categories to where
genes are annotated.
Methods: We present three novel methodologies for the functional
assessment of time-course microarray data. i) maSigFun derives from the
maSigPro method, a regression-based strategy to model time-dependent
expression patterns and identify genes with differences across series.
maSigFun fits a regression model for groups of genes labeled by a
functional class and selects those categories which have a significant
model. ii) PCA-maSigFun fits a PCA model of each functional
class-defined expression matrix to extract orthogonal patterns of
expression change, which are then assessed for their fit to a
time-dependent regression model. iii) ASCA-functional uses the ASCA
model to rank genes according to their correlation to principal time
expression patterns and assess functional enrichment on a GSA fashion.
We used simulated and experimental datasets to study these novel
approaches. Results were compared to alternative methodologies.
Results: Synthetic and experimental data showed that the different
methods are able to capture different aspects of the relationship
between genes, functions and co-expression that are biologically
meaningful. The methods should not be considered as competitive but they
provide different insights into the molecular and functional dynamic
events taking place within the biological system under study.
24.
Conesa, A.; Bro, R.; Garcia-Garcia, F.; Prats, J. M.; Gotz, S.; Kjeldahl, K.; Montaner, D.; Dopazo, J.
Direct functional assessment of the composite phenotype through multivariate projection strategies Journal Article
In: GENOMICS, vol. 92, no. 6, pp. 373-383, 2008, ISSN: 0888-7543.
@article{ISI:000261460100001,
title = {Direct functional assessment of the composite phenotype through
multivariate projection strategies},
author = { A. Conesa and R. Bro and F. Garcia-Garcia and J. M. Prats and S. Gotz and K. Kjeldahl and D. Montaner and J. Dopazo},
url = {http://dx.doi.org/10.1016/j.ygeno.2008.05.015},
doi = {10.1016/j.ygeno.2008.05.015},
issn = {0888-7543},
year = {2008},
date = {2008-12-01},
journal = {GENOMICS},
volume = {92},
number = {6},
pages = {373-383},
abstract = {We present a novel approach for the analysis of transcriptomics; data
that integrates functional annotation of gene sets with expression
values in a multivariate fashion, and directly assesses the relation of
functional features to a multivariate space of response phenotypical
variables. Multivariate projection methods are used to obtain new
correlated variables for a set of genes that share a given function.
These new functional variables are then related to the response
variables of interest. The analysis of the principal directions of the
multivariate regression allows for the identification of gene function
features correlated with the phenotype. Two different transcriptomics
studies are used to illustrate the statistical and interpretative
aspects of the methodology. We demonstrate the superiority of the
proposed method over equivalent approaches. (C) 2008 Elsevier Inc. All
rights reserved.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
We present a novel approach for the analysis of transcriptomics; data
that integrates functional annotation of gene sets with expression
values in a multivariate fashion, and directly assesses the relation of
functional features to a multivariate space of response phenotypical
variables. Multivariate projection methods are used to obtain new
correlated variables for a set of genes that share a given function.
These new functional variables are then related to the response
variables of interest. The analysis of the principal directions of the
multivariate regression allows for the identification of gene function
features correlated with the phenotype. Two different transcriptomics
studies are used to illustrate the statistical and interpretative
aspects of the methodology. We demonstrate the superiority of the
proposed method over equivalent approaches. (C) 2008 Elsevier Inc. All
rights reserved.
that integrates functional annotation of gene sets with expression
values in a multivariate fashion, and directly assesses the relation of
functional features to a multivariate space of response phenotypical
variables. Multivariate projection methods are used to obtain new
correlated variables for a set of genes that share a given function.
These new functional variables are then related to the response
variables of interest. The analysis of the principal directions of the
multivariate regression allows for the identification of gene function
features correlated with the phenotype. Two different transcriptomics
studies are used to illustrate the statistical and interpretative
aspects of the methodology. We demonstrate the superiority of the
proposed method over equivalent approaches. (C) 2008 Elsevier Inc. All
rights reserved.
23.
Hoogerwerf, W. A.; Sinha, M.; Conesa, A.; Luxon, B. A.; Shahinian, V. B.; Cornelissen, G.; Halberg, F.; Bostwick, J.; Timm, J.; Cassone, V. M.
Transcriptional Profiling of mRNA Expression in the Mouse Distal Colon Journal Article
In: GASTROENTEROLOGY, vol. 135, no. 6, pp. 2019-2029, 2008, ISSN: 0016-5085.
@article{ISI:000261762200064,
title = {Transcriptional Profiling of mRNA Expression in the Mouse Distal Colon},
author = { W. A. Hoogerwerf and M. Sinha and A. Conesa and B. A. Luxon and V. B. Shahinian and G. Cornelissen and F. Halberg and J. Bostwick and J. Timm and V. M. Cassone},
url = {http://dx.doi.org/10.1053/j.gastro.2008.08.048},
doi = {10.1053/j.gastro.2008.08.048},
issn = {0016-5085},
year = {2008},
date = {2008-12-01},
journal = {GASTROENTEROLOGY},
volume = {135},
number = {6},
pages = {2019-2029},
abstract = {Background & Aims: intestinal epithelial cells and the myenteric plexus
of the mouse gastrointestinal tract contain a circadian clock-based
intrinsic timekeeping system. Because disruption of the biological clock
has been associated with increased susceptibility to colon cancer and
gastrointestinal symptoms, we aimed to identify rhythmically expressed
genes in the mouse distal colon. Methods: Microarray analysis was used
to identify genes that were rhythmically expressed over a 24-hour
light/dark cycle. The transcripts were then classified according to
expression pattern, function, and association with physiologic and
pathophysiologic processes of the colon. Results: A circadian gene
expression pattern was detected in approximately 3.7% of distal.
colonic genes. A large percentage of these genes were involved in cell
signaling, differentiation, and proliferation and cell death. Of all the
rhythmically expressed genes in the mouse colon, approximately 7%
(64/906) have been associated with colorectal cancer formation (eg, B-cell leukemia/lymphoma-2 [Bcl2]) and 1.8% (18/906) with various
colonic functions such as motility and secretion (eg, vasoactive
intestinal polypeptide, cystic fibrosis transmembrane conductance
regulator). Conclusions: A subset of genes in the murine colon follows a
rhythmic expression pattern. These findings may have significant
implications for colonic physiology and pathophysiology.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Background & Aims: intestinal epithelial cells and the myenteric plexus
of the mouse gastrointestinal tract contain a circadian clock-based
intrinsic timekeeping system. Because disruption of the biological clock
has been associated with increased susceptibility to colon cancer and
gastrointestinal symptoms, we aimed to identify rhythmically expressed
genes in the mouse distal colon. Methods: Microarray analysis was used
to identify genes that were rhythmically expressed over a 24-hour
light/dark cycle. The transcripts were then classified according to
expression pattern, function, and association with physiologic and
pathophysiologic processes of the colon. Results: A circadian gene
expression pattern was detected in approximately 3.7% of distal.
colonic genes. A large percentage of these genes were involved in cell
signaling, differentiation, and proliferation and cell death. Of all the
rhythmically expressed genes in the mouse colon, approximately 7%
(64/906) have been associated with colorectal cancer formation (eg, B-cell leukemia/lymphoma-2 [Bcl2]) and 1.8% (18/906) with various
colonic functions such as motility and secretion (eg, vasoactive
intestinal polypeptide, cystic fibrosis transmembrane conductance
regulator). Conclusions: A subset of genes in the murine colon follows a
rhythmic expression pattern. These findings may have significant
implications for colonic physiology and pathophysiology.
of the mouse gastrointestinal tract contain a circadian clock-based
intrinsic timekeeping system. Because disruption of the biological clock
has been associated with increased susceptibility to colon cancer and
gastrointestinal symptoms, we aimed to identify rhythmically expressed
genes in the mouse distal colon. Methods: Microarray analysis was used
to identify genes that were rhythmically expressed over a 24-hour
light/dark cycle. The transcripts were then classified according to
expression pattern, function, and association with physiologic and
pathophysiologic processes of the colon. Results: A circadian gene
expression pattern was detected in approximately 3.7% of distal.
colonic genes. A large percentage of these genes were involved in cell
signaling, differentiation, and proliferation and cell death. Of all the
rhythmically expressed genes in the mouse colon, approximately 7%
(64/906) have been associated with colorectal cancer formation (eg, B-cell leukemia/lymphoma-2 [Bcl2]) and 1.8% (18/906) with various
colonic functions such as motility and secretion (eg, vasoactive
intestinal polypeptide, cystic fibrosis transmembrane conductance
regulator). Conclusions: A subset of genes in the murine colon follows a
rhythmic expression pattern. These findings may have significant
implications for colonic physiology and pathophysiology.
22.
Stierum, R.; Conesa, A.; Heijne, W.; van Ommen, B.; Junker, K.; Scott, M. P.; Price, R. J.; Meredith, C.; Lake, B. G.; Groten, J.
In: FOOD AND CHEMICAL TOXICOLOGY, vol. 46, no. 8, pp. 2616-2628, 2008, ISSN: 0278-6915.
@article{ISI:000258440100004,
title = {Transcriptome analysis provides new insights into liver changes induced
in the rat upon dietary administration of the food additives butylated
hydroxytoluene, curcumin, propyl gallate and thiabendazole},
author = { R. Stierum and A. Conesa and W. Heijne and B. van Ommen and K. Junker and M. P. Scott and R. J. Price and C. Meredith and B. G. Lake and J. Groten},
url = {http://dx.doi.org/10.1016/j.fct.2008.04.019},
doi = {10.1016/j.fct.2008.04.019},
issn = {0278-6915},
year = {2008},
date = {2008-08-01},
journal = {FOOD AND CHEMICAL TOXICOLOGY},
volume = {46},
number = {8},
pages = {2616-2628},
abstract = {Transcriptomics was performed to gain insight into mechanisms of food
additives butylated hydroxytoluene (BHT), curcumin (CC), propyl gallate
(PG), and thiabendazole (TB), additives for which interactions in the
liver can not be excluded. Additives were administered in diets for 28
days to Sprague-Dawley rats and cDNA microarray experiments were
performed on hepatic RNA. BHT induced changes in the expression of 10
genes, including phase I (CYP2B1/2: CYP3A9; CYP2C6) and phase II
metabolism (GST mu 2). The CYP2B1/2 and GST expression findings were
confirmed by real time RT-PCR, western blotting, and increased GST
activity towards DCNB. CC altered the expression of 12 genes. Three out
of these were related to peroxisomes (phytanoyl-CoA dioxygenase, enoyl-CoA hydratase; CYP4A3). Increased cyanide insensitive
palmitoyl-CoA oxidation was observed, suggesting that CC is a weak
peroxisome proliferator. TB changed the expression of 12 genes, including CYP1A2. In line, CYP1A2 protein expression was increased. The
expression level of five genes, associated with p53 was found to change
upon TB treatment, including p53 itself, GADD45 alpha, DN-7, protein
kinase C beta and serum albumin. These array experiments led to the
novel finding that TB is capable of inducing p53 at the protein level, at least at the highest dose levels employed above the current NOAEL.
The expression of eight genes changed upon PG administration. This study
shows the value of gene expression profiling in food toxicology in terms
of generating novel hypotheses on the mechanisms of action of food
additives in relation to pathology. (C) 2008 Elsevier Ltd. All rights
reserved.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Transcriptomics was performed to gain insight into mechanisms of food
additives butylated hydroxytoluene (BHT), curcumin (CC), propyl gallate
(PG), and thiabendazole (TB), additives for which interactions in the
liver can not be excluded. Additives were administered in diets for 28
days to Sprague-Dawley rats and cDNA microarray experiments were
performed on hepatic RNA. BHT induced changes in the expression of 10
genes, including phase I (CYP2B1/2: CYP3A9; CYP2C6) and phase II
metabolism (GST mu 2). The CYP2B1/2 and GST expression findings were
confirmed by real time RT-PCR, western blotting, and increased GST
activity towards DCNB. CC altered the expression of 12 genes. Three out
of these were related to peroxisomes (phytanoyl-CoA dioxygenase, enoyl-CoA hydratase; CYP4A3). Increased cyanide insensitive
palmitoyl-CoA oxidation was observed, suggesting that CC is a weak
peroxisome proliferator. TB changed the expression of 12 genes, including CYP1A2. In line, CYP1A2 protein expression was increased. The
expression level of five genes, associated with p53 was found to change
upon TB treatment, including p53 itself, GADD45 alpha, DN-7, protein
kinase C beta and serum albumin. These array experiments led to the
novel finding that TB is capable of inducing p53 at the protein level, at least at the highest dose levels employed above the current NOAEL.
The expression of eight genes changed upon PG administration. This study
shows the value of gene expression profiling in food toxicology in terms
of generating novel hypotheses on the mechanisms of action of food
additives in relation to pathology. (C) 2008 Elsevier Ltd. All rights
reserved.
additives butylated hydroxytoluene (BHT), curcumin (CC), propyl gallate
(PG), and thiabendazole (TB), additives for which interactions in the
liver can not be excluded. Additives were administered in diets for 28
days to Sprague-Dawley rats and cDNA microarray experiments were
performed on hepatic RNA. BHT induced changes in the expression of 10
genes, including phase I (CYP2B1/2: CYP3A9; CYP2C6) and phase II
metabolism (GST mu 2). The CYP2B1/2 and GST expression findings were
confirmed by real time RT-PCR, western blotting, and increased GST
activity towards DCNB. CC altered the expression of 12 genes. Three out
of these were related to peroxisomes (phytanoyl-CoA dioxygenase, enoyl-CoA hydratase; CYP4A3). Increased cyanide insensitive
palmitoyl-CoA oxidation was observed, suggesting that CC is a weak
peroxisome proliferator. TB changed the expression of 12 genes, including CYP1A2. In line, CYP1A2 protein expression was increased. The
expression level of five genes, associated with p53 was found to change
upon TB treatment, including p53 itself, GADD45 alpha, DN-7, protein
kinase C beta and serum albumin. These array experiments led to the
novel finding that TB is capable of inducing p53 at the protein level, at least at the highest dose levels employed above the current NOAEL.
The expression of eight genes changed upon PG administration. This study
shows the value of gene expression profiling in food toxicology in terms
of generating novel hypotheses on the mechanisms of action of food
additives in relation to pathology. (C) 2008 Elsevier Ltd. All rights
reserved.
21.
Tarraga, J.; Medina, I.; Carbonell, J.; Huerta-Cepas, J.; Minguez, P.; Alloza, E.; Al-Shahrour, F.; Vegas-Azcarate, S.; Goetz, S.; Escobar, P.; Garcia-Garcia, F.; Conesa, A.; Montaner, D.; Dopazo, J.
GEPAS, a web-based tool for microarray data analysis and interpretation Journal Article
In: NUCLEIC ACIDS RESEARCH, vol. 36, no. S, pp. W308-W314, 2008, ISSN: 0305-1048.
@article{ISI:000258142300058,
title = {GEPAS, a web-based tool for microarray data analysis and interpretation},
author = { J. Tarraga and I. Medina and J. Carbonell and J. Huerta-Cepas and P. Minguez and E. Alloza and F. Al-Shahrour and S. Vegas-Azcarate and S. Goetz and P. Escobar and F. Garcia-Garcia and A. Conesa and D. Montaner and J. Dopazo},
url = {http://dx.doi.org/10.1093/nar/gkn303},
doi = {10.1093/nar/gkn303},
issn = {0305-1048},
year = {2008},
date = {2008-07-01},
journal = {NUCLEIC ACIDS RESEARCH},
volume = {36},
number = {S},
pages = {W308-W314},
abstract = {Gene Expression Profile Analysis Suite (GEPAS) is one of the most
complete and extensively used web-based packages for microarray data
analysis. During its more than 5 years of activity it has continuously
been updated to keep pace with the state-of-the-art in the changing
microarray data analysis arena. GEPAS offers diverse analysis options
that include well established as well as novel algorithms for
normalization, gene selection, class prediction, clustering and
functional profiling of the experiment. New options for time-course (or
dose-response) experiments, microarray-based class prediction, new
clustering methods and new tests for differential expression have been
included. The new pipeliner module allows automating the execution of
sequential analysis steps by means of a simple but powerful graphic
interface. An extensive re-engineering of GEPAS has been carried out
which includes the use of web services and Web 2.0 technology features, a new user interface with persistent sessions and a new extended
database of gene identifiers. GEPAS is nowadays the most quoted web tool
in its field and it is extensively used by researchers of many countries
and its records indicate an average usage rate of 500 experiments per
day. GEPAS, is available at http://www.gepas.org.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Gene Expression Profile Analysis Suite (GEPAS) is one of the most
complete and extensively used web-based packages for microarray data
analysis. During its more than 5 years of activity it has continuously
been updated to keep pace with the state-of-the-art in the changing
microarray data analysis arena. GEPAS offers diverse analysis options
that include well established as well as novel algorithms for
normalization, gene selection, class prediction, clustering and
functional profiling of the experiment. New options for time-course (or
dose-response) experiments, microarray-based class prediction, new
clustering methods and new tests for differential expression have been
included. The new pipeliner module allows automating the execution of
sequential analysis steps by means of a simple but powerful graphic
interface. An extensive re-engineering of GEPAS has been carried out
which includes the use of web services and Web 2.0 technology features, a new user interface with persistent sessions and a new extended
database of gene identifiers. GEPAS is nowadays the most quoted web tool
in its field and it is extensively used by researchers of many countries
and its records indicate an average usage rate of 500 experiments per
day. GEPAS, is available at http://www.gepas.org.
complete and extensively used web-based packages for microarray data
analysis. During its more than 5 years of activity it has continuously
been updated to keep pace with the state-of-the-art in the changing
microarray data analysis arena. GEPAS offers diverse analysis options
that include well established as well as novel algorithms for
normalization, gene selection, class prediction, clustering and
functional profiling of the experiment. New options for time-course (or
dose-response) experiments, microarray-based class prediction, new
clustering methods and new tests for differential expression have been
included. The new pipeliner module allows automating the execution of
sequential analysis steps by means of a simple but powerful graphic
interface. An extensive re-engineering of GEPAS has been carried out
which includes the use of web services and Web 2.0 technology features, a new user interface with persistent sessions and a new extended
database of gene identifiers. GEPAS is nowadays the most quoted web tool
in its field and it is extensively used by researchers of many countries
and its records indicate an average usage rate of 500 experiments per
day. GEPAS, is available at http://www.gepas.org.
20.
Al-Shahrour, F.; Carbonell, J.; Minguez, P.; Goetz, S.; Conesa, A.; Tarrraga, J.; Medina, I.; Alloza, E.; Montaner, D.; Dopazo, J.
Babelomics: advanced functional profiling of transcriptomics, proteomics and genomics experiments Journal Article
In: NUCLEIC ACIDS RESEARCH, vol. 36, no. S, pp. W341-W346, 2008, ISSN: 0305-1048.
@article{ISI:000258142300064,
title = {Babelomics: advanced functional profiling of transcriptomics, proteomics
and genomics experiments},
author = { F. Al-Shahrour and J. Carbonell and P. Minguez and S. Goetz and A. Conesa and J. Tarrraga and I. Medina and E. Alloza and D. Montaner and J. Dopazo},
url = {http://dx.doi.org/10.1093/nar/gkn318},
doi = {10.1093/nar/gkn318},
issn = {0305-1048},
year = {2008},
date = {2008-07-01},
journal = {NUCLEIC ACIDS RESEARCH},
volume = {36},
number = {S},
pages = {W341-W346},
abstract = {We present a new version of Babelomics, a complete suite of web tools
for the functional profiling of genome scale experiments, with new and
improved methods as well as more types of functional definitions.
Babelomics includes different flavours of conventional functional
enrichment methods as well as more advanced gene set analysis methods
that makes it a unique tool among the similar resources available. In
addition to the well-known functional definitions (GO, KEGG), Babelomics
includes new ones such as Biocarta pathways or text mining-derived
functional terms. Regulatory modules implemented include transcriptional
control (Transfac, CisRed) and other levels of regulation such as
miRNA-mediated interference. Moreover, Babelomics allows for
sub-selection of terms in order to test more focused hypothesis. Also
gene annotation correspondence tables can be imported, which allows
testing with user-defined functional modules. Finally, a tool for the de
novo functional annotation of sequences has been included in the system.
This allows using yet unannotated organisms in the program. Babelomics
has been extensively re-engineered and now it includes the use of web
services and Web 2.0 technology features, a new user interface with
persistent sessions and a new extended database of gene identifiers.
Babelomics is available at http://www.babelomics.org.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
We present a new version of Babelomics, a complete suite of web tools
for the functional profiling of genome scale experiments, with new and
improved methods as well as more types of functional definitions.
Babelomics includes different flavours of conventional functional
enrichment methods as well as more advanced gene set analysis methods
that makes it a unique tool among the similar resources available. In
addition to the well-known functional definitions (GO, KEGG), Babelomics
includes new ones such as Biocarta pathways or text mining-derived
functional terms. Regulatory modules implemented include transcriptional
control (Transfac, CisRed) and other levels of regulation such as
miRNA-mediated interference. Moreover, Babelomics allows for
sub-selection of terms in order to test more focused hypothesis. Also
gene annotation correspondence tables can be imported, which allows
testing with user-defined functional modules. Finally, a tool for the de
novo functional annotation of sequences has been included in the system.
This allows using yet unannotated organisms in the program. Babelomics
has been extensively re-engineered and now it includes the use of web
services and Web 2.0 technology features, a new user interface with
persistent sessions and a new extended database of gene identifiers.
Babelomics is available at http://www.babelomics.org.
for the functional profiling of genome scale experiments, with new and
improved methods as well as more types of functional definitions.
Babelomics includes different flavours of conventional functional
enrichment methods as well as more advanced gene set analysis methods
that makes it a unique tool among the similar resources available. In
addition to the well-known functional definitions (GO, KEGG), Babelomics
includes new ones such as Biocarta pathways or text mining-derived
functional terms. Regulatory modules implemented include transcriptional
control (Transfac, CisRed) and other levels of regulation such as
miRNA-mediated interference. Moreover, Babelomics allows for
sub-selection of terms in order to test more focused hypothesis. Also
gene annotation correspondence tables can be imported, which allows
testing with user-defined functional modules. Finally, a tool for the de
novo functional annotation of sequences has been included in the system.
This allows using yet unannotated organisms in the program. Babelomics
has been extensively re-engineered and now it includes the use of web
services and Web 2.0 technology features, a new user interface with
persistent sessions and a new extended database of gene identifiers.
Babelomics is available at http://www.babelomics.org.
19.
Botton, A.; Galla, G.; Conesa, A.; Bachem, C.; Ramina, A.; Barcaccia, G.
Large-scale Gene Ontology analysis of plant transcriptome-derived sequences retrieved by AFLP technology Journal Article
In: BMC GENOMICS, vol. 9, 2008, ISSN: 1471-2164.
@article{ISI:000258552300001,
title = {Large-scale Gene Ontology analysis of plant transcriptome-derived
sequences retrieved by AFLP technology},
author = { A. Botton and G. Galla and A. Conesa and C. Bachem and A. Ramina and G. Barcaccia},
url = {http://dx.doi.org/10.1186/1471-2164-9-347},
doi = {10.1186/1471-2164-9-347},
issn = {1471-2164},
year = {2008},
date = {2008-07-01},
journal = {BMC GENOMICS},
volume = {9},
abstract = {Background: After 10-year-use of AFLP (Amplified Fragment Length
Polymorphism) technology for DNA fingerprinting and mRNA profiling, large repertories of genome- and transcriptome-derived sequences are
available in public databases for model, crop and tree species. AFLP
marker systems have been and are being extensively exploited for genome
scanning and gene mapping, as well as cDNA-AFLP for transcriptome
profiling and differentially expressed gene cloning. The evaluation, annotation and classification of genomic markers and expressed
transcripts would be of great utility for both functional genomics and
systems biology research in plants. This may be achieved by means of the
Gene Ontology (GO), consisting in three structured vocabularies (i.e.
ontologies) describing genes, transcripts and proteins of any organism
in terms of their associated cellular component, biological process and
molecular function in a species-independent manner. In this paper, the
functional annotation of about 8,000 AFLP-derived ESTs retrieved in the
NCBI databases was carried out by using GO terminology.
Results: Descriptive statistics on the type, size and nature of gene
sequences obtained by means of AFLP technology were calculated. The gene
products associated with mRNA transcripts were then classified according
to the three main GO vocabularies. A comparison of the functional
content of cDNA-AFLP records was also performed by splitting the
sequence dataset into monocots and dicots and by comparing them to all
annotated ESTs of Arabidopsis and rice, respectively. On the whole, the
statistical parameters adopted for the in silico AFLP-derived
transcriptome-anchored sequence analysis proved to be critical for
obtaining reliable GO results. Such an exhaustive annotation may offer a
suitable platform for functional genomics, particularly useful in
non-model species.
Conclusion: Reliable GO annotations of AFLP-derived sequences can be
gathered through the optimization of the experimental steps and the
statistical parameters adopted. The Blast2GO software was shown to
represent a comprehensive bioinformatics solution for an
annotation-based functional analysis. According to the whole set of GO
annotations, the AFLP technology generates thorough information for
angiosperm gene products and shares common features across angiosperm
species and families. The utility of this technology for structural and
functional genomics in plants can be implemented by serial annotation
analyses of genome- anchored fragments and organ/tissue-specific
repertories of transcriptome-derived fragments.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Background: After 10-year-use of AFLP (Amplified Fragment Length
Polymorphism) technology for DNA fingerprinting and mRNA profiling, large repertories of genome- and transcriptome-derived sequences are
available in public databases for model, crop and tree species. AFLP
marker systems have been and are being extensively exploited for genome
scanning and gene mapping, as well as cDNA-AFLP for transcriptome
profiling and differentially expressed gene cloning. The evaluation, annotation and classification of genomic markers and expressed
transcripts would be of great utility for both functional genomics and
systems biology research in plants. This may be achieved by means of the
Gene Ontology (GO), consisting in three structured vocabularies (i.e.
ontologies) describing genes, transcripts and proteins of any organism
in terms of their associated cellular component, biological process and
molecular function in a species-independent manner. In this paper, the
functional annotation of about 8,000 AFLP-derived ESTs retrieved in the
NCBI databases was carried out by using GO terminology.
Results: Descriptive statistics on the type, size and nature of gene
sequences obtained by means of AFLP technology were calculated. The gene
products associated with mRNA transcripts were then classified according
to the three main GO vocabularies. A comparison of the functional
content of cDNA-AFLP records was also performed by splitting the
sequence dataset into monocots and dicots and by comparing them to all
annotated ESTs of Arabidopsis and rice, respectively. On the whole, the
statistical parameters adopted for the in silico AFLP-derived
transcriptome-anchored sequence analysis proved to be critical for
obtaining reliable GO results. Such an exhaustive annotation may offer a
suitable platform for functional genomics, particularly useful in
non-model species.
Conclusion: Reliable GO annotations of AFLP-derived sequences can be
gathered through the optimization of the experimental steps and the
statistical parameters adopted. The Blast2GO software was shown to
represent a comprehensive bioinformatics solution for an
annotation-based functional analysis. According to the whole set of GO
annotations, the AFLP technology generates thorough information for
angiosperm gene products and shares common features across angiosperm
species and families. The utility of this technology for structural and
functional genomics in plants can be implemented by serial annotation
analyses of genome- anchored fragments and organ/tissue-specific
repertories of transcriptome-derived fragments.
Polymorphism) technology for DNA fingerprinting and mRNA profiling, large repertories of genome- and transcriptome-derived sequences are
available in public databases for model, crop and tree species. AFLP
marker systems have been and are being extensively exploited for genome
scanning and gene mapping, as well as cDNA-AFLP for transcriptome
profiling and differentially expressed gene cloning. The evaluation, annotation and classification of genomic markers and expressed
transcripts would be of great utility for both functional genomics and
systems biology research in plants. This may be achieved by means of the
Gene Ontology (GO), consisting in three structured vocabularies (i.e.
ontologies) describing genes, transcripts and proteins of any organism
in terms of their associated cellular component, biological process and
molecular function in a species-independent manner. In this paper, the
functional annotation of about 8,000 AFLP-derived ESTs retrieved in the
NCBI databases was carried out by using GO terminology.
Results: Descriptive statistics on the type, size and nature of gene
sequences obtained by means of AFLP technology were calculated. The gene
products associated with mRNA transcripts were then classified according
to the three main GO vocabularies. A comparison of the functional
content of cDNA-AFLP records was also performed by splitting the
sequence dataset into monocots and dicots and by comparing them to all
annotated ESTs of Arabidopsis and rice, respectively. On the whole, the
statistical parameters adopted for the in silico AFLP-derived
transcriptome-anchored sequence analysis proved to be critical for
obtaining reliable GO results. Such an exhaustive annotation may offer a
suitable platform for functional genomics, particularly useful in
non-model species.
Conclusion: Reliable GO annotations of AFLP-derived sequences can be
gathered through the optimization of the experimental steps and the
statistical parameters adopted. The Blast2GO software was shown to
represent a comprehensive bioinformatics solution for an
annotation-based functional analysis. According to the whole set of GO
annotations, the AFLP technology generates thorough information for
angiosperm gene products and shares common features across angiosperm
species and families. The utility of this technology for structural and
functional genomics in plants can be implemented by serial annotation
analyses of genome- anchored fragments and organ/tissue-specific
repertories of transcriptome-derived fragments.
18.
Gotz, S.; Garcia-Gomez, J. M.; Terol, J.; Williams, T. D.; Nagaraj, S. H.; Nueda, M. J.; Robles, M.; Talon, M.; Dopazo, J.; Conesa, A.
High-throughput functional annotation and data mining with the Blast2GO suite Journal Article
In: NUCLEIC ACIDS RESEARCH, vol. 36, no. 10, pp. 3420-3435, 2008, ISSN: 0305-1048.
@article{ISI:000257183200025,
title = {High-throughput functional annotation and data mining with the Blast2GO
suite},
author = { S. Gotz and J. M. Garcia-Gomez and J. Terol and T. D. Williams and S. H. Nagaraj and M. J. Nueda and M. Robles and M. Talon and J. Dopazo and A. Conesa},
url = {http://dx.doi.org/10.1093/nar/gkn176},
doi = {10.1093/nar/gkn176},
issn = {0305-1048},
year = {2008},
date = {2008-06-01},
journal = {NUCLEIC ACIDS RESEARCH},
volume = {36},
number = {10},
pages = {3420-3435},
abstract = {Functional genomics technologies have been widely adopted in the
biological research of both model and non-model species. An efficient
functional annotation of DNA or protein sequences is a major requirement
for the successful application of these approaches as functional
information on gene products is often the key to the interpretation of
experimental results. Therefore, there is an increasing need for
bioinformatics resources which are able to cope with large amount of
sequence data, produce valuable annotation results and are easily
accessible to laboratories where functional genomics projects are being
undertaken. We present the Blast2GO suite as an integrated and
biologist-oriented solution for the high-throughput and automatic
functional annotation of DNA or protein sequences based on the Gene
Ontology vocabulary. The most outstanding Blast2GO features are: (i) the
combination of various annotation strategies and tools controlling type
and intensity of annotation, (ii) the numerous graphical features such
as the interactive GO-graph visualization for gene-set function
profiling or descriptive charts, (iii) the general sequence management
features and (iv) high-throughput capabilities. We used the Blast2GO
framework to carry out a detailed analysis of annotation behaviour
through homology transfer and its impact in functional genomics
research. Our aim is to offer biologists useful information to take into
account when addressing the task of functionally characterizing their
sequence data.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Functional genomics technologies have been widely adopted in the
biological research of both model and non-model species. An efficient
functional annotation of DNA or protein sequences is a major requirement
for the successful application of these approaches as functional
information on gene products is often the key to the interpretation of
experimental results. Therefore, there is an increasing need for
bioinformatics resources which are able to cope with large amount of
sequence data, produce valuable annotation results and are easily
accessible to laboratories where functional genomics projects are being
undertaken. We present the Blast2GO suite as an integrated and
biologist-oriented solution for the high-throughput and automatic
functional annotation of DNA or protein sequences based on the Gene
Ontology vocabulary. The most outstanding Blast2GO features are: (i) the
combination of various annotation strategies and tools controlling type
and intensity of annotation, (ii) the numerous graphical features such
as the interactive GO-graph visualization for gene-set function
profiling or descriptive charts, (iii) the general sequence management
features and (iv) high-throughput capabilities. We used the Blast2GO
framework to carry out a detailed analysis of annotation behaviour
through homology transfer and its impact in functional genomics
research. Our aim is to offer biologists useful information to take into
account when addressing the task of functionally characterizing their
sequence data.
biological research of both model and non-model species. An efficient
functional annotation of DNA or protein sequences is a major requirement
for the successful application of these approaches as functional
information on gene products is often the key to the interpretation of
experimental results. Therefore, there is an increasing need for
bioinformatics resources which are able to cope with large amount of
sequence data, produce valuable annotation results and are easily
accessible to laboratories where functional genomics projects are being
undertaken. We present the Blast2GO suite as an integrated and
biologist-oriented solution for the high-throughput and automatic
functional annotation of DNA or protein sequences based on the Gene
Ontology vocabulary. The most outstanding Blast2GO features are: (i) the
combination of various annotation strategies and tools controlling type
and intensity of annotation, (ii) the numerous graphical features such
as the interactive GO-graph visualization for gene-set function
profiling or descriptive charts, (iii) the general sequence management
features and (iv) high-throughput capabilities. We used the Blast2GO
framework to carry out a detailed analysis of annotation behaviour
through homology transfer and its impact in functional genomics
research. Our aim is to offer biologists useful information to take into
account when addressing the task of functionally characterizing their
sequence data.
17.
Agudo, M.; Perez-Marin, M. C.; Loenngren, U.; Sobrado, P.; Conesa, A.; Canovas, I.; Salinas-Navarro, M.; Miralles-Imperial, J.; Hallbook, F.; Vidal-Sanz, M.
Time course profiling of the retinal transcriptome after optic nerve transection and optic nerve crush Journal Article
In: MOLECULAR VISION, vol. 14, no. 126, pp. 1050-1063, 2008, ISSN: 1090-0535.
@article{ISI:000257750100001,
title = {Time course profiling of the retinal transcriptome after optic nerve
transection and optic nerve crush},
author = { M. Agudo and M. C. Perez-Marin and U. Loenngren and P. Sobrado and A. Conesa and I. Canovas and M. Salinas-Navarro and J. Miralles-Imperial and F. Hallbook and M. Vidal-Sanz},
issn = {1090-0535},
year = {2008},
date = {2008-06-01},
journal = {MOLECULAR VISION},
volume = {14},
number = {126},
pages = {1050-1063},
abstract = {Purpose: A time-course analysis of gene regulation in the adult rat
retina after intraorbital nerve crush (IONC) and intraorbital nerve
transection (IONT).
Methods: RNA was extracted from adult rat retinas undergoing either IONT
or IONC at increasing times post-lesion. Affymetrix RAE230.2 arrays were
hybridized and analyzed. Statistically regulated genes were annotated
and functionally clustered. Arrays were validated by means of quantative
reverse transcription polymerase chain reaction (qRT-PCR) on ten
regulated genes at two times post-lesion. Western blotting and
immunohistofluorescence for four pro-apoptotic proteins were performed
on naive and injured retinas. Finally, custom signaling maps for IONT-
and IONC-induced death response were generated (MetaCore, Genego Inc.).
Results: Here we show that over time, 3,219 sequences were regulated
after IONT and 1,996 after IONC. Out of the total of regulated
sequences, 1,078 were commonly regulated by both injuries.
Interestingly, while IONT mainly triggers a gene upregulation-sustained
over time, IONC causes a transitory downregulation. Functional
clustering identified the regulation of high interest biologic
processes, most importantly cell death wherein apoptosis was the most
significant cluster. Ten death-related genes upregulated by both
injuries were used for array validation by means of qRT-PCR. In
addition, western blotting and immunohistofluorescence of total and
active Caspase 3 (Casp3), tumor necrosis factor receptor type 1
associated death domain (TRADD), tumor necrosis factor receptor
superfamily member 1a (TNFR1a), and c-fos were performed to confirm
their protein regulation and expression pattern in nave and injured
retinas. These analyses demonstrated that for these genes, protein
regulation followed transcriptional regulation and that these
proapoptotic proteins were expressed by retinal ganglion cells (RGCs).
MetaCore-based death-signaling maps show that several apoptotic cascades
were regulated in the retina following optic nerve injury and highlight
the similarities and differences between IONT and IONC in cell death
profiling.
Conclusions: This comprehensive time course retinal transcriptome study
comparing IONT and IONC lesions provides a unique valuable tool to
understand the molecular mechanisms underlying optic nerve injury and to
design neuroprotective protocols.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Purpose: A time-course analysis of gene regulation in the adult rat
retina after intraorbital nerve crush (IONC) and intraorbital nerve
transection (IONT).
Methods: RNA was extracted from adult rat retinas undergoing either IONT
or IONC at increasing times post-lesion. Affymetrix RAE230.2 arrays were
hybridized and analyzed. Statistically regulated genes were annotated
and functionally clustered. Arrays were validated by means of quantative
reverse transcription polymerase chain reaction (qRT-PCR) on ten
regulated genes at two times post-lesion. Western blotting and
immunohistofluorescence for four pro-apoptotic proteins were performed
on naive and injured retinas. Finally, custom signaling maps for IONT-
and IONC-induced death response were generated (MetaCore, Genego Inc.).
Results: Here we show that over time, 3,219 sequences were regulated
after IONT and 1,996 after IONC. Out of the total of regulated
sequences, 1,078 were commonly regulated by both injuries.
Interestingly, while IONT mainly triggers a gene upregulation-sustained
over time, IONC causes a transitory downregulation. Functional
clustering identified the regulation of high interest biologic
processes, most importantly cell death wherein apoptosis was the most
significant cluster. Ten death-related genes upregulated by both
injuries were used for array validation by means of qRT-PCR. In
addition, western blotting and immunohistofluorescence of total and
active Caspase 3 (Casp3), tumor necrosis factor receptor type 1
associated death domain (TRADD), tumor necrosis factor receptor
superfamily member 1a (TNFR1a), and c-fos were performed to confirm
their protein regulation and expression pattern in nave and injured
retinas. These analyses demonstrated that for these genes, protein
regulation followed transcriptional regulation and that these
proapoptotic proteins were expressed by retinal ganglion cells (RGCs).
MetaCore-based death-signaling maps show that several apoptotic cascades
were regulated in the retina following optic nerve injury and highlight
the similarities and differences between IONT and IONC in cell death
profiling.
Conclusions: This comprehensive time course retinal transcriptome study
comparing IONT and IONC lesions provides a unique valuable tool to
understand the molecular mechanisms underlying optic nerve injury and to
design neuroprotective protocols.
retina after intraorbital nerve crush (IONC) and intraorbital nerve
transection (IONT).
Methods: RNA was extracted from adult rat retinas undergoing either IONT
or IONC at increasing times post-lesion. Affymetrix RAE230.2 arrays were
hybridized and analyzed. Statistically regulated genes were annotated
and functionally clustered. Arrays were validated by means of quantative
reverse transcription polymerase chain reaction (qRT-PCR) on ten
regulated genes at two times post-lesion. Western blotting and
immunohistofluorescence for four pro-apoptotic proteins were performed
on naive and injured retinas. Finally, custom signaling maps for IONT-
and IONC-induced death response were generated (MetaCore, Genego Inc.).
Results: Here we show that over time, 3,219 sequences were regulated
after IONT and 1,996 after IONC. Out of the total of regulated
sequences, 1,078 were commonly regulated by both injuries.
Interestingly, while IONT mainly triggers a gene upregulation-sustained
over time, IONC causes a transitory downregulation. Functional
clustering identified the regulation of high interest biologic
processes, most importantly cell death wherein apoptosis was the most
significant cluster. Ten death-related genes upregulated by both
injuries were used for array validation by means of qRT-PCR. In
addition, western blotting and immunohistofluorescence of total and
active Caspase 3 (Casp3), tumor necrosis factor receptor type 1
associated death domain (TRADD), tumor necrosis factor receptor
superfamily member 1a (TNFR1a), and c-fos were performed to confirm
their protein regulation and expression pattern in nave and injured
retinas. These analyses demonstrated that for these genes, protein
regulation followed transcriptional regulation and that these
proapoptotic proteins were expressed by retinal ganglion cells (RGCs).
MetaCore-based death-signaling maps show that several apoptotic cascades
were regulated in the retina following optic nerve injury and highlight
the similarities and differences between IONT and IONC in cell death
profiling.
Conclusions: This comprehensive time course retinal transcriptome study
comparing IONT and IONC lesions provides a unique valuable tool to
understand the molecular mechanisms underlying optic nerve injury and to
design neuroprotective protocols.
16.
Levin, A. M.; de Vries, R. P.; Conesa, A.; de Bekker, C.; Talon, M.; Menke, H. H.; van Peij, N. N. M. E.; Wosten, H. A. B.
Spatial differentiation in the vegetative mycelium of Aspergillus niger Journal Article
In: EUKARYOTIC CELL, vol. 6, no. 12, pp. 2311-2322, 2007, ISSN: 1535-9778.
@article{ISI:000251896100016,
title = {Spatial differentiation in the vegetative mycelium of Aspergillus niger},
author = { A. M. Levin and R. P. de Vries and A. Conesa and C. de Bekker and M. Talon and H. H. Menke and N. N. M. E. van Peij and H. A. B. Wosten},
url = {http://dx.doi.org/10.1128/EC.00244-07},
doi = {10.1128/EC.00244-07},
issn = {1535-9778},
year = {2007},
date = {2007-12-01},
journal = {EUKARYOTIC CELL},
volume = {6},
number = {12},
pages = {2311-2322},
abstract = {Fungal mycelia are exposed to heterogenic substrates. The substrate in
the central part of the colony has been (partly) degraded, whereas it is
still unexplored at the periphery of the mycelium. We here assessed
whether substrate heterogeneity is a main determinant of spatial gene
expression in colonies of Aspergillus niger. This question was addressed
by analyzing whole-genome gene expression in five concentric zones of
7-day-old maltose- and xylose-grown colonies. Expression profiles at the
periphery and the center were clearly different. More than 25% of the
active genes showed twofold differences in expression between the inner
and outermost zones of the colony. Moreover, 9% of the genes were
expressed in only one of the five concentric zones, showing that a
considerable part of the genome is active in a restricted part of the
colony only. Statistical analysis of expression profiles of colonies
that had either been or not been transferred to fresh xylose-containing
medium showed that differential expression in a colony is due to the
heterogeneity of the medium (e.g., genes involved in secretion, genes
encoding proteases, and genes involved in xylose metabolism) as well as
to medium-independent mechanisms (e.g., genes involved in nitrate
metabolism and genes involved in cell wall synthesis and modification).
Thus, we conclude that the mycelia of 7-day-old colonies of A. niger are
highly differentiated. This conclusion is also indicated by the fact
that distinct zones of the colony grow and secrete proteins, even after
transfer to fresh medium.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Fungal mycelia are exposed to heterogenic substrates. The substrate in
the central part of the colony has been (partly) degraded, whereas it is
still unexplored at the periphery of the mycelium. We here assessed
whether substrate heterogeneity is a main determinant of spatial gene
expression in colonies of Aspergillus niger. This question was addressed
by analyzing whole-genome gene expression in five concentric zones of
7-day-old maltose- and xylose-grown colonies. Expression profiles at the
periphery and the center were clearly different. More than 25% of the
active genes showed twofold differences in expression between the inner
and outermost zones of the colony. Moreover, 9% of the genes were
expressed in only one of the five concentric zones, showing that a
considerable part of the genome is active in a restricted part of the
colony only. Statistical analysis of expression profiles of colonies
that had either been or not been transferred to fresh xylose-containing
medium showed that differential expression in a colony is due to the
heterogeneity of the medium (e.g., genes involved in secretion, genes
encoding proteases, and genes involved in xylose metabolism) as well as
to medium-independent mechanisms (e.g., genes involved in nitrate
metabolism and genes involved in cell wall synthesis and modification).
Thus, we conclude that the mycelia of 7-day-old colonies of A. niger are
highly differentiated. This conclusion is also indicated by the fact
that distinct zones of the colony grow and secrete proteins, even after
transfer to fresh medium.
the central part of the colony has been (partly) degraded, whereas it is
still unexplored at the periphery of the mycelium. We here assessed
whether substrate heterogeneity is a main determinant of spatial gene
expression in colonies of Aspergillus niger. This question was addressed
by analyzing whole-genome gene expression in five concentric zones of
7-day-old maltose- and xylose-grown colonies. Expression profiles at the
periphery and the center were clearly different. More than 25% of the
active genes showed twofold differences in expression between the inner
and outermost zones of the colony. Moreover, 9% of the genes were
expressed in only one of the five concentric zones, showing that a
considerable part of the genome is active in a restricted part of the
colony only. Statistical analysis of expression profiles of colonies
that had either been or not been transferred to fresh xylose-containing
medium showed that differential expression in a colony is due to the
heterogeneity of the medium (e.g., genes involved in secretion, genes
encoding proteases, and genes involved in xylose metabolism) as well as
to medium-independent mechanisms (e.g., genes involved in nitrate
metabolism and genes involved in cell wall synthesis and modification).
Thus, we conclude that the mycelia of 7-day-old colonies of A. niger are
highly differentiated. This conclusion is also indicated by the fact
that distinct zones of the colony grow and secrete proteins, even after
transfer to fresh medium.
15.
Gandia, M.; Conesa, A.; Ancillo, G.; Gadea, J.; Forment, J.; Pallas, V.; Flores, R.; Duran-Vila, N.; Moreno, P.; Guerri, J.
Transcriptional response of Citrus aurantifolia to infection by Citrus tristeza virus Journal Article
In: VIROLOGY, vol. 367, no. 2, pp. 298-306, 2007, ISSN: 0042-6822.
@article{ISI:000250162900007,
title = {Transcriptional response of Citrus aurantifolia to infection by Citrus
tristeza virus},
author = { M. Gandia and A. Conesa and G. Ancillo and J. Gadea and J. Forment and V. Pallas and R. Flores and N. Duran-Vila and P. Moreno and J. Guerri},
url = {http://dx.doi.org/10.1016/j.virol.2007.05.025},
doi = {10.1016/j.virol.2007.05.025},
issn = {0042-6822},
year = {2007},
date = {2007-10-01},
journal = {VIROLOGY},
volume = {367},
number = {2},
pages = {298-306},
abstract = {Changes in gene expression of Mexican lime plants in response to
infection with a severe (T305) or a mild (T385) isolate of Citrus
tristeza virus (CTV) were analyzed using a cDNA microarray containing
12,672 probes to 6875 different citrus genes. Statistically significant
(P < 0.01) expression changes of 334 genes were detected in response to
infection with isolate T305, whereas infection with T385 induced no
significant change. Induced genes included 145 without significant
similarity with known sequences and 189 that were classified in seven
functional categories. Genes related with response to stress and defense
were the main category and included 28% of the genes induced. Selected
transcription changes detected by microarray analysis were confirmed by
quantitative real-time RT-PCR. Changes detected in the transcriptome
upon infecting lime with T305 may be associated either with symptom
expression, with a strain-specific defense mechanism, or with a general
response to stress. (c) 2007 Elsevier Inc. All rights reserved.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Changes in gene expression of Mexican lime plants in response to
infection with a severe (T305) or a mild (T385) isolate of Citrus
tristeza virus (CTV) were analyzed using a cDNA microarray containing
12,672 probes to 6875 different citrus genes. Statistically significant
(P < 0.01) expression changes of 334 genes were detected in response to
infection with isolate T305, whereas infection with T385 induced no
significant change. Induced genes included 145 without significant
similarity with known sequences and 189 that were classified in seven
functional categories. Genes related with response to stress and defense
were the main category and included 28% of the genes induced. Selected
transcription changes detected by microarray analysis were confirmed by
quantitative real-time RT-PCR. Changes detected in the transcriptome
upon infecting lime with T305 may be associated either with symptom
expression, with a strain-specific defense mechanism, or with a general
response to stress. (c) 2007 Elsevier Inc. All rights reserved.
infection with a severe (T305) or a mild (T385) isolate of Citrus
tristeza virus (CTV) were analyzed using a cDNA microarray containing
12,672 probes to 6875 different citrus genes. Statistically significant
(P < 0.01) expression changes of 334 genes were detected in response to
infection with isolate T305, whereas infection with T385 induced no
significant change. Induced genes included 145 without significant
similarity with known sequences and 189 that were classified in seven
functional categories. Genes related with response to stress and defense
were the main category and included 28% of the genes induced. Selected
transcription changes detected by microarray analysis were confirmed by
quantitative real-time RT-PCR. Changes detected in the transcriptome
upon infecting lime with T305 may be associated either with symptom
expression, with a strain-specific defense mechanism, or with a general
response to stress. (c) 2007 Elsevier Inc. All rights reserved.
14.
Nueda, M. J.; Conesa, A.; Westerhuis, J. A.; Hoefsloot, H. C. J.; Smilde, A. K.; Talon, M.; Ferrer, A.
Discovering gene expression patterns in time course microarray experiments by ANOVA-SCA Journal Article
In: BIOINFORMATICS, vol. 23, no. 14, pp. 1792-1800, 2007, ISSN: 1367-4803.
@article{ISI:000249248300011,
title = {Discovering gene expression patterns in time course microarray
experiments by ANOVA-SCA},
author = { M. J. Nueda and A. Conesa and J. A. Westerhuis and H. C. J. Hoefsloot and A. K. Smilde and M. Talon and A. Ferrer},
url = {http://dx.doi.org/10.1093/bioinformatics/btm251},
doi = {10.1093/bioinformatics/btm251},
issn = {1367-4803},
year = {2007},
date = {2007-07-01},
journal = {BIOINFORMATICS},
volume = {23},
number = {14},
pages = {1792-1800},
abstract = {Motivation: Designed microarray experiments are used to investigate the
effects that controlled experimental factors have on gene expression and
learn about the transcriptional responses associated with external
variables. In these datasets, signals of interest coexist with varying
sources of unwanted noise in a framework of (co)relation among the
measured variables and with the different levels of the studied factors.
Discovering experimentally relevant transcriptional changes require
methodologies that take all these elements into account.
Results: In this work, we develop the application of the Analysis of
variance-simultaneous component analysis (ANOVA-SCA) Smilde et al, Bioinformatics, (2005) to the analysis of multiple series time course
microarray data as an example of multifactorial gene expression
profiling experiments. We denoted this implementation as ASCA-genes. We
show how the combination of ANOVA-modeling and a dimension reduction
technique is effective in extracting targeted signals from data
by-passing structural noise. The methodology is valuable for identifying
main and secondary responses associated with the experimental factors
and spotting relevant experimental conditions. We additionally propose a
novel approach for gene selection in the context of the relation of
individual transcriptional patterns to global gene expression signals.
We demonstrate the methodology on both real and synthetic datasets.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Motivation: Designed microarray experiments are used to investigate the
effects that controlled experimental factors have on gene expression and
learn about the transcriptional responses associated with external
variables. In these datasets, signals of interest coexist with varying
sources of unwanted noise in a framework of (co)relation among the
measured variables and with the different levels of the studied factors.
Discovering experimentally relevant transcriptional changes require
methodologies that take all these elements into account.
Results: In this work, we develop the application of the Analysis of
variance-simultaneous component analysis (ANOVA-SCA) Smilde et al, Bioinformatics, (2005) to the analysis of multiple series time course
microarray data as an example of multifactorial gene expression
profiling experiments. We denoted this implementation as ASCA-genes. We
show how the combination of ANOVA-modeling and a dimension reduction
technique is effective in extracting targeted signals from data
by-passing structural noise. The methodology is valuable for identifying
main and secondary responses associated with the experimental factors
and spotting relevant experimental conditions. We additionally propose a
novel approach for gene selection in the context of the relation of
individual transcriptional patterns to global gene expression signals.
We demonstrate the methodology on both real and synthetic datasets.
effects that controlled experimental factors have on gene expression and
learn about the transcriptional responses associated with external
variables. In these datasets, signals of interest coexist with varying
sources of unwanted noise in a framework of (co)relation among the
measured variables and with the different levels of the studied factors.
Discovering experimentally relevant transcriptional changes require
methodologies that take all these elements into account.
Results: In this work, we develop the application of the Analysis of
variance-simultaneous component analysis (ANOVA-SCA) Smilde et al, Bioinformatics, (2005) to the analysis of multiple series time course
microarray data as an example of multifactorial gene expression
profiling experiments. We denoted this implementation as ASCA-genes. We
show how the combination of ANOVA-modeling and a dimension reduction
technique is effective in extracting targeted signals from data
by-passing structural noise. The methodology is valuable for identifying
main and secondary responses associated with the experimental factors
and spotting relevant experimental conditions. We additionally propose a
novel approach for gene selection in the context of the relation of
individual transcriptional patterns to global gene expression signals.
We demonstrate the methodology on both real and synthetic datasets.
13.
Terol, J.; Conesa, A.; Colmenero, J. M.; Cercos, M.; Tadeo, F.; Agusti, J.; Alos, E.; Andres, F.; Soler, G.; Brumos, J.; Iglesias, D. J.; Gotz, S.; Legaz, F.; Argout, X.; Courtois, B.; Ollitrault, P.; Dossat, C.; Wincker, P.; Morillon, R.; Talon, M.
Analysis of 13000 unique Citrus clusters associated with fruit quality, production and salinity tolerance Journal Article
In: BMC GENOMICS, vol. 8, 2007, ISSN: 1471-2164.
@article{ISI:000244326200001,
title = {Analysis of 13000 unique Citrus clusters associated with fruit quality, production and salinity tolerance},
author = { J. Terol and A. Conesa and J. M. Colmenero and M. Cercos and F. Tadeo and J. Agusti and E. Alos and F. Andres and G. Soler and J. Brumos and D. J. Iglesias and S. Gotz and F. Legaz and X. Argout and B. Courtois and P. Ollitrault and C. Dossat and P. Wincker and R. Morillon and M. Talon},
url = {http://dx.doi.org/10.1186/1471-2164-8-31},
doi = {10.1186/1471-2164-8-31},
issn = {1471-2164},
year = {2007},
date = {2007-01-01},
journal = {BMC GENOMICS},
volume = {8},
abstract = {Background: Improvement of Citrus, the most economically important fruit
crop in the world, is extremely slow and inherently costly because of
the long-term nature of tree breeding and an unusual combination of
reproductive characteristics. Aside from disease resistance, major
commercial traits in Citrus are improved fruit quality, higher yield and
tolerance to environmental stresses, especially salinity.
Results: A normalized full length and 9 standard cDNA libraries were
generated, representing particular treatments and tissues from selected
varieties ( Citrus clementina and C. sinensis) and rootstocks ( C.
reshni, and C. sinenis x Poncirus trifoliata) differing in fruit
quality, resistance to abscission, and tolerance to salinity. The goal
of this work was to provide a large expressed sequence tag ( EST)
collection enriched with transcripts related to these well appreciated
agronomical traits. Towards this end, more than 54000 ESTs derived from
these libraries were analyzed and annotated. Assembly of 52626 useful
sequences generated 15664 putative transcription units distributed in
7120 contigs, and 8544 singletons. BLAST annotation produced significant
hits for more than 80% of the hypothetical transcription units and
suggested that 647 of these might be Citrus specific unigenes. The
unigene set, composed of similar to 13000 putative different
transcripts, including more than 5000 novel Citrus genes, was assigned
with putative functions based on similarity, GO annotations and protein
domains.
Conclusion: Comparative genomics with Arabidopsis revealed the presence
of putative conserved orthologs and single copy genes in Citrus and also
the occurrence of both gene duplication events and increased number of
genes for specific pathways. In addition, phylogenetic analysis
performed on the ammonium transporter family and glycosyl transferase
family 20 suggested the existence of Citrus paralogs. Analysis of the
Citrus gene space showed that the most important metabolic pathways
known to affect fruit quality were represented in the unigene set.
Overall, the similarity analyses indicated that the sequences of the
genes belonging to these varieties and rootstocks were essentially
identical, suggesting that the differential behaviour of these species
cannot be attributed to major sequence divergences. This Citrus EST
assembly contributes both crucial information to discover genes of
agronomical interest and tools for genetic and genomic analyses, such as
the development of new markers and microarrays.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Background: Improvement of Citrus, the most economically important fruit
crop in the world, is extremely slow and inherently costly because of
the long-term nature of tree breeding and an unusual combination of
reproductive characteristics. Aside from disease resistance, major
commercial traits in Citrus are improved fruit quality, higher yield and
tolerance to environmental stresses, especially salinity.
Results: A normalized full length and 9 standard cDNA libraries were
generated, representing particular treatments and tissues from selected
varieties ( Citrus clementina and C. sinensis) and rootstocks ( C.
reshni, and C. sinenis x Poncirus trifoliata) differing in fruit
quality, resistance to abscission, and tolerance to salinity. The goal
of this work was to provide a large expressed sequence tag ( EST)
collection enriched with transcripts related to these well appreciated
agronomical traits. Towards this end, more than 54000 ESTs derived from
these libraries were analyzed and annotated. Assembly of 52626 useful
sequences generated 15664 putative transcription units distributed in
7120 contigs, and 8544 singletons. BLAST annotation produced significant
hits for more than 80% of the hypothetical transcription units and
suggested that 647 of these might be Citrus specific unigenes. The
unigene set, composed of similar to 13000 putative different
transcripts, including more than 5000 novel Citrus genes, was assigned
with putative functions based on similarity, GO annotations and protein
domains.
Conclusion: Comparative genomics with Arabidopsis revealed the presence
of putative conserved orthologs and single copy genes in Citrus and also
the occurrence of both gene duplication events and increased number of
genes for specific pathways. In addition, phylogenetic analysis
performed on the ammonium transporter family and glycosyl transferase
family 20 suggested the existence of Citrus paralogs. Analysis of the
Citrus gene space showed that the most important metabolic pathways
known to affect fruit quality were represented in the unigene set.
Overall, the similarity analyses indicated that the sequences of the
genes belonging to these varieties and rootstocks were essentially
identical, suggesting that the differential behaviour of these species
cannot be attributed to major sequence divergences. This Citrus EST
assembly contributes both crucial information to discover genes of
agronomical interest and tools for genetic and genomic analyses, such as
the development of new markers and microarrays.
crop in the world, is extremely slow and inherently costly because of
the long-term nature of tree breeding and an unusual combination of
reproductive characteristics. Aside from disease resistance, major
commercial traits in Citrus are improved fruit quality, higher yield and
tolerance to environmental stresses, especially salinity.
Results: A normalized full length and 9 standard cDNA libraries were
generated, representing particular treatments and tissues from selected
varieties ( Citrus clementina and C. sinensis) and rootstocks ( C.
reshni, and C. sinenis x Poncirus trifoliata) differing in fruit
quality, resistance to abscission, and tolerance to salinity. The goal
of this work was to provide a large expressed sequence tag ( EST)
collection enriched with transcripts related to these well appreciated
agronomical traits. Towards this end, more than 54000 ESTs derived from
these libraries were analyzed and annotated. Assembly of 52626 useful
sequences generated 15664 putative transcription units distributed in
7120 contigs, and 8544 singletons. BLAST annotation produced significant
hits for more than 80% of the hypothetical transcription units and
suggested that 647 of these might be Citrus specific unigenes. The
unigene set, composed of similar to 13000 putative different
transcripts, including more than 5000 novel Citrus genes, was assigned
with putative functions based on similarity, GO annotations and protein
domains.
Conclusion: Comparative genomics with Arabidopsis revealed the presence
of putative conserved orthologs and single copy genes in Citrus and also
the occurrence of both gene duplication events and increased number of
genes for specific pathways. In addition, phylogenetic analysis
performed on the ammonium transporter family and glycosyl transferase
family 20 suggested the existence of Citrus paralogs. Analysis of the
Citrus gene space showed that the most important metabolic pathways
known to affect fruit quality were represented in the unigene set.
Overall, the similarity analyses indicated that the sequences of the
genes belonging to these varieties and rootstocks were essentially
identical, suggesting that the differential behaviour of these species
cannot be attributed to major sequence divergences. This Citrus EST
assembly contributes both crucial information to discover genes of
agronomical interest and tools for genetic and genomic analyses, such as
the development of new markers and microarrays.
12.
Williams, T. D.; Diab, A. M.; George, S. G.; Godfrey, R. E.; Sabine, V.; Conesa, A.; Minchin, S. D.; Watts, P. C.; Chipman, J. K.
In: ENVIRONMENTAL SCIENCE & TECHNOLOGY, vol. 40, no. 20, pp. 6479-6488, 2006, ISSN: 0013-936X.
@article{ISI:000241192600050,
title = {Development of the GENIPOL European flounder (Platichthys flesus)
microarray and determination of temporal transcriptional responses to
cadmium at low dose.},
author = { T. D. Williams and A. M. Diab and S. G. George and R. E. Godfrey and V. Sabine and A. Conesa and S. D. Minchin and P. C. Watts and J. K. Chipman},
url = {http://dx.doi.org/10.1021/es061142h},
doi = {10.1021/es061142h},
issn = {0013-936X},
year = {2006},
date = {2006-10-01},
journal = {ENVIRONMENTAL SCIENCE & TECHNOLOGY},
volume = {40},
number = {20},
pages = {6479-6488},
abstract = {We have constructed a high density, 13 270-clone cDNA array for the
sentinel fish species European flounder (Platichthys flesus), combining
clones from suppressive subtractive hybridization and a liver cDNA
library; DNA sequences of 5211 clones were determined. Fish were treated
by single intraperitoneal injection with 50 micrograms cadmium chloride
per kilogram body weight, a dose relevant to environmental exposures, and hepatic gene expression changes were determined at 1, 2, 4, 8, and
16 days postinjection in comparison to saline-treated controls. Gene
expression responses were confirmed by real-time reverse transcription
polymerase chain reaction (RT-PCR). Blast2GO gene ontology analysis
highlighted a general induction of the unfolded protein response, response to oxidative stress, protein synthesis, transport, and
degradation pathways, while apoptosis, cell cycle, cytoskeleton, and
cytokine genes were also affected. Transcript levels of cytochrome P450
1A (CYP1A) were repressed and vitellogenin altered, real-time PCR showed
induction of metallothionein. We thus describe the establishment of a
useful resource for ecotoxicogenomics and the determination of the
temporal molecular responses to cadmium, a prototypical heavy metal
pollutant.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
We have constructed a high density, 13 270-clone cDNA array for the
sentinel fish species European flounder (Platichthys flesus), combining
clones from suppressive subtractive hybridization and a liver cDNA
library; DNA sequences of 5211 clones were determined. Fish were treated
by single intraperitoneal injection with 50 micrograms cadmium chloride
per kilogram body weight, a dose relevant to environmental exposures, and hepatic gene expression changes were determined at 1, 2, 4, 8, and
16 days postinjection in comparison to saline-treated controls. Gene
expression responses were confirmed by real-time reverse transcription
polymerase chain reaction (RT-PCR). Blast2GO gene ontology analysis
highlighted a general induction of the unfolded protein response, response to oxidative stress, protein synthesis, transport, and
degradation pathways, while apoptosis, cell cycle, cytoskeleton, and
cytokine genes were also affected. Transcript levels of cytochrome P450
1A (CYP1A) were repressed and vitellogenin altered, real-time PCR showed
induction of metallothionein. We thus describe the establishment of a
useful resource for ecotoxicogenomics and the determination of the
temporal molecular responses to cadmium, a prototypical heavy metal
pollutant.
sentinel fish species European flounder (Platichthys flesus), combining
clones from suppressive subtractive hybridization and a liver cDNA
library; DNA sequences of 5211 clones were determined. Fish were treated
by single intraperitoneal injection with 50 micrograms cadmium chloride
per kilogram body weight, a dose relevant to environmental exposures, and hepatic gene expression changes were determined at 1, 2, 4, 8, and
16 days postinjection in comparison to saline-treated controls. Gene
expression responses were confirmed by real-time reverse transcription
polymerase chain reaction (RT-PCR). Blast2GO gene ontology analysis
highlighted a general induction of the unfolded protein response, response to oxidative stress, protein synthesis, transport, and
degradation pathways, while apoptosis, cell cycle, cytoskeleton, and
cytokine genes were also affected. Transcript levels of cytochrome P450
1A (CYP1A) were repressed and vitellogenin altered, real-time PCR showed
induction of metallothionein. We thus describe the establishment of a
useful resource for ecotoxicogenomics and the determination of the
temporal molecular responses to cadmium, a prototypical heavy metal
pollutant.
11.
Conesa, A.; Nueda, M.; Ferrer, A.; Talon, M.
maSigPro: a method to identify significantly differential expression profiles in time-course microarray experiments Journal Article
In: BIOINFORMATICS, vol. 22, no. 9, pp. 1096-1102, 2006, ISSN: 1367-4803.
@article{ISI:000236997600009,
title = {maSigPro: a method to identify significantly differential expression
profiles in time-course microarray experiments},
author = { A. Conesa and M. Nueda and A. Ferrer and M. Talon},
url = {http://dx.doi.org/10.1093/bioinformatics/btl056},
doi = {10.1093/bioinformatics/btl056},
issn = {1367-4803},
year = {2006},
date = {2006-05-01},
journal = {BIOINFORMATICS},
volume = {22},
number = {9},
pages = {1096-1102},
abstract = {Motivation: Multi-series time-course microarray experiments are useful
approaches for exploring biological processes. In this type of
experiments, the researcher is frequently interested in studying gene
expression changes along time and in evaluating trend differences
between the various experimental groups. The large amount of data, multiplicity of experimental conditions and the dynamic nature of the
experiments poses great challenges to data analysis.
Results: In this work, we propose a statistical procedure to identify
genes that show different gene expression profiles across analytical
groups in time-course experiments. The method is a two-regression step
approach where the experimental groups are identified by dummy
variables. The procedure first adjusts a global regression model with
all the defined variables to identify differentially expressed genes, and in second a variable selection strategy is applied to study
differences between groups and to find statistically significant
different profiles. The methodology is illustrated on both a real and a
simulated microarray dataset.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Motivation: Multi-series time-course microarray experiments are useful
approaches for exploring biological processes. In this type of
experiments, the researcher is frequently interested in studying gene
expression changes along time and in evaluating trend differences
between the various experimental groups. The large amount of data, multiplicity of experimental conditions and the dynamic nature of the
experiments poses great challenges to data analysis.
Results: In this work, we propose a statistical procedure to identify
genes that show different gene expression profiles across analytical
groups in time-course experiments. The method is a two-regression step
approach where the experimental groups are identified by dummy
variables. The procedure first adjusts a global regression model with
all the defined variables to identify differentially expressed genes, and in second a variable selection strategy is applied to study
differences between groups and to find statistically significant
different profiles. The methodology is illustrated on both a real and a
simulated microarray dataset.
approaches for exploring biological processes. In this type of
experiments, the researcher is frequently interested in studying gene
expression changes along time and in evaluating trend differences
between the various experimental groups. The large amount of data, multiplicity of experimental conditions and the dynamic nature of the
experiments poses great challenges to data analysis.
Results: In this work, we propose a statistical procedure to identify
genes that show different gene expression profiles across analytical
groups in time-course experiments. The method is a two-regression step
approach where the experimental groups are identified by dummy
variables. The procedure first adjusts a global regression model with
all the defined variables to identify differentially expressed genes, and in second a variable selection strategy is applied to study
differences between groups and to find statistically significant
different profiles. The methodology is illustrated on both a real and a
simulated microarray dataset.
10.
Conesa, A.; Gotz, S.; Garcia-Gomez, J.; Terol, J.; Talon, M.; Robles, M.
Blast2GO: a universal tool for annotation, visualization and analysis in functional genomics research Journal Article
In: BIOINFORMATICS, vol. 21, no. 18, pp. 3674-3676, 2005, ISSN: 1367-4803.
@article{ISI:000231694600016,
title = {Blast2GO: a universal tool for annotation, visualization and analysis in
functional genomics research},
author = { A. Conesa and S. Gotz and J. Garcia-Gomez and J. Terol and M. Talon and M. Robles},
url = {http://dx.doi.org/10.1093/bioinformatics/bti610},
doi = {10.1093/bioinformatics/bti610},
issn = {1367-4803},
year = {2005},
date = {2005-09-01},
journal = {BIOINFORMATICS},
volume = {21},
number = {18},
pages = {3674-3676},
abstract = {We present here Blast2GO (B2G), a research tool designed with the main
purpose of enabling Gene Ontology (GO) based data mining on sequence
data for which no GO annotation is yet available. B2G joints in one
application GO annotation based on similarity searches with statistical
analysis and highlighted visualization on directed acyclic graphs. This
tool offers a suitable platform for functional genomics research in
non-model species. B2G is an intuitive and interactive desktop
application that allows monitoring and comprehension of the whole
annotation and analysis process.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
We present here Blast2GO (B2G), a research tool designed with the main
purpose of enabling Gene Ontology (GO) based data mining on sequence
data for which no GO annotation is yet available. B2G joints in one
application GO annotation based on similarity searches with statistical
analysis and highlighted visualization on directed acyclic graphs. This
tool offers a suitable platform for functional genomics research in
non-model species. B2G is an intuitive and interactive desktop
application that allows monitoring and comprehension of the whole
annotation and analysis process.
purpose of enabling Gene Ontology (GO) based data mining on sequence
data for which no GO annotation is yet available. B2G joints in one
application GO annotation based on similarity searches with statistical
analysis and highlighted visualization on directed acyclic graphs. This
tool offers a suitable platform for functional genomics research in
non-model species. B2G is an intuitive and interactive desktop
application that allows monitoring and comprehension of the whole
annotation and analysis process.
9.
Forment, J.; Gadea, J.; Huerta, L.; Abizanda, L.; Agusti, J.; Alamar, S.; Alos, E.; Andres, F.; Arribas, R.; Beltran, J.; Berbel, A.; Blazquez, M.; Brumos, J.; Canas, L.; Cercos, M.; Colmenero-Flores, J.; Conesa, A.; Estables, B.; Gandia, M.; Garcia-Martinez, J.; Gimeno, J.; Gisbert, A.; Gomez, G.; Gonzalez-Candelas, L.; Granell, A.; Guerri, J.; Lafuente, M.; Madueno, F.; Marcos, J.; Marques, M.; Martinez, F.; Martinez-Godoy, M.; Miralles, S.; Moreno, P.; Navarro, L.; Pallas, V.; Perez-Amador, M.; Perez-Valle, J.; Pons, C.; Rodrigo, I.; Rodriguez, P.; Royo, C.; Serrano, R.; Soler, G.; Tadeo, F.; Talon, M.; Terol, J.; Trenor, M.; Vaello, L.; Vicente, O.; Vidal, C.; Zacarias, L.; Conejero, V.
Development of a citrus genome-wide EST collection and cDNA microarray as resources for genomic studies Journal Article
In: PLANT MOLECULAR BIOLOGY, vol. 57, no. 3, pp. 375-391, 2005, ISSN: 0167-4412.
@article{ISI:000229478400005,
title = {Development of a citrus genome-wide EST collection and cDNA microarray
as resources for genomic studies},
author = { J. Forment and J. Gadea and L. Huerta and L. Abizanda and J. Agusti and S. Alamar and E. Alos and F. Andres and R. Arribas and J. Beltran and A. Berbel and M. Blazquez and J. Brumos and L. Canas and M. Cercos and J. Colmenero-Flores and A. Conesa and B. Estables and M. Gandia and J. Garcia-Martinez and J. Gimeno and A. Gisbert and G. Gomez and L. Gonzalez-Candelas and A. Granell and J. Guerri and M. Lafuente and F. Madueno and J. Marcos and M. Marques and F. Martinez and M. Martinez-Godoy and S. Miralles and P. Moreno and L. Navarro and V. Pallas and M. Perez-Amador and J. Perez-Valle and C. Pons and I. Rodrigo and P. Rodriguez and C. Royo and R. Serrano and G. Soler and F. Tadeo and M. Talon and J. Terol and M. Trenor and L. Vaello and O. Vicente and C. Vidal and L. Zacarias and V. Conejero},
url = {http://dx.doi.org/10.1007/s11103-004-7926-1},
doi = {10.1007/s11103-004-7926-1},
issn = {0167-4412},
year = {2005},
date = {2005-02-01},
journal = {PLANT MOLECULAR BIOLOGY},
volume = {57},
number = {3},
pages = {375-391},
abstract = {A functional genomics project has been initiated to approach the
molecular characterization of the main biological and agronomical traits
of citrus. As a key part of this project, a citrus EST collection has
been generated from 25 cDNA libraries covering different tissues, developmental stages and stress conditions. The collection includes a
total of 22,635 high-quality ESTs, grouped in 11,836 putative unigenes, which represent at least one third of the estimated number of genes in
the citrus genome. Functional annotation of unigenes which have
Arabidopsis orthologues (68% of all unigenes) revealed gene
representation in every major functional category, suggesting that a
genome-wide EST collection was obtained. A Citrus clementina Hort. ex
Tan. cv. Clemenules genomic library, that will contribute to further
characterization of relevant genes, has also been constructed. To
initiate the analysis of citrus transcriptome, we have developed a cDNA
microarray containing 12,672 probes corresponding to 6875 putative
unigenes of the collection. Technical characterization of the microarray
showed high intra- and inter-array reproducibility, as well as a good
range of sensitivity. We have also validated gene expression data
achieved with this microarray through an independent technique such as
RNA gel blot analysis.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
A functional genomics project has been initiated to approach the
molecular characterization of the main biological and agronomical traits
of citrus. As a key part of this project, a citrus EST collection has
been generated from 25 cDNA libraries covering different tissues, developmental stages and stress conditions. The collection includes a
total of 22,635 high-quality ESTs, grouped in 11,836 putative unigenes, which represent at least one third of the estimated number of genes in
the citrus genome. Functional annotation of unigenes which have
Arabidopsis orthologues (68% of all unigenes) revealed gene
representation in every major functional category, suggesting that a
genome-wide EST collection was obtained. A Citrus clementina Hort. ex
Tan. cv. Clemenules genomic library, that will contribute to further
characterization of relevant genes, has also been constructed. To
initiate the analysis of citrus transcriptome, we have developed a cDNA
microarray containing 12,672 probes corresponding to 6875 putative
unigenes of the collection. Technical characterization of the microarray
showed high intra- and inter-array reproducibility, as well as a good
range of sensitivity. We have also validated gene expression data
achieved with this microarray through an independent technique such as
RNA gel blot analysis.
molecular characterization of the main biological and agronomical traits
of citrus. As a key part of this project, a citrus EST collection has
been generated from 25 cDNA libraries covering different tissues, developmental stages and stress conditions. The collection includes a
total of 22,635 high-quality ESTs, grouped in 11,836 putative unigenes, which represent at least one third of the estimated number of genes in
the citrus genome. Functional annotation of unigenes which have
Arabidopsis orthologues (68% of all unigenes) revealed gene
representation in every major functional category, suggesting that a
genome-wide EST collection was obtained. A Citrus clementina Hort. ex
Tan. cv. Clemenules genomic library, that will contribute to further
characterization of relevant genes, has also been constructed. To
initiate the analysis of citrus transcriptome, we have developed a cDNA
microarray containing 12,672 probes corresponding to 6875 putative
unigenes of the collection. Technical characterization of the microarray
showed high intra- and inter-array reproducibility, as well as a good
range of sensitivity. We have also validated gene expression data
achieved with this microarray through an independent technique such as
RNA gel blot analysis.